The purpose of this study is to investigate three seemingly independent aspects of the growth and biology of human colon carcinoma in an attempt to relate them to each other and to the clinical extent and course of the disease. The areas to be investigated include the following: (1) The release of circulating antigen by the tumor as a potential mechanism of escape from immunologic control. (2) Elaboration of proteolytic enzymes by primary and metastatic colon carcinoma as a mechanism in the development of metastases. (3) Tissue levels of cyclic AMP, cyclic GMP, and cyclic CMP in normal colon mucosa, primary and metastatic carcinoma, as factors in general tumor activity and growth control. The course of tumors will be expanded to include the Minneapolis V.A. Hospital and attempts will be made to get more fresh specimens for cyclic nucleotide study. The presence of circulating antigen-antibody complexes will be confirmed or refuted, investigating the potential artifacts and other immunological factors outlined above. If such complexes are indeed found to be present, attempts will be made to physically separate them from other serum components and then to split the complexes into their antigen and antibody subunits, both of which may be obtained in this way in a relatively pure form. Specimens of human colon tumors which are currently being stored in a frozen state will be assayed for collagenase activity using the procedures developed as part of this study. Serum samples from the same patients will also be assayed for circulating enzyme. Following analysis of enzyme activity the active tissues will be pooled and an attempt will be made to purify and characterize the collagenase.